公开(公告)号：WO2017107052A1

公开(公告)日：2017-06-29

申请号：PCT/CN2015/098251

申请日：2015-12-22

Applicant: MERCK SHARP & DOHME CORP. ,  BERGER, Raphaelle ,  CHEN, Yi-Heng ,  LI, Guoqing ,  GARFUNKEL, Joie ,  LI, Hong ,  MIAO, Shouwu ,  RAGHAVAN, Subharekha ,  SMITH, Cameron J. ,  WHITEHEAD, Alan ,  ZHANG, Rui ,  ZHANG, Yong ,  FU, Jianmin ,  JI, Gang ,  JIANG, Falong

Inventor： BERGER, Raphaelle ,  CHEN, Yi-Heng ,  LI, Guoqing ,  GARFUNKEL, Joie ,  LI, Hong ,  MIAO, Shouwu ,  RAGHAVAN, Subharekha ,  SMITH, Cameron J. ,  WHITEHEAD, Alan ,  ZHANG, Rui ,  ZHANG, Yong ,  FU, Jianmin ,  JI, Gang ,  JIANG, Falong

IPC: C07D487/04 ,  A61K31/519 ,  A61P9/00 ,  A61P3/10

CPC classification number: C07D487/04 ,  A61K31/519 ,  A61K45/06 ,  C07D519/00

Abstract: The invention provides compounds of the Formula (I) or a pharmaceutically acceptable salts thereof, wherein X, Y, Z, R 1 , R 2 , R 4 , R a , and the subscripts m, p, and q are as described herein. The compounds or their pharmaceutically acceptable salts can modulate the body's production of cyclic guanosine monophosphate ("cGMP"), and are generally suitable for the therapy and prophylaxis of diseases which are associated with a disturbed cGMP balance. The invention also provides pharmaceutical compositions which comprise compounds of Formula (I) or pharmaceutically acceptable salts thereof. The invention also relates to methods for use of the compounds or their pharmaceutically acceptable salts in the therapy and prophylaxis of the abovementioned diseases and for preparing pharmaceuticals for this purpose.

Abstract translation: 本发明提供式（I）的化合物或其药学上可接受的盐，其中X，Y，Z，R 1，R 2， R 4，R a和下标m，p和q如本文所述。 所述化合物或其药学上可接受的盐可调节身体产生环鸟苷单磷酸（“cGMP”），并且通常适用于治疗和预防与扰乱的cGMP平衡有关的疾病。 本发明还提供了包含式（I）化合物或其药学上可接受的盐的药物组合物。 本发明还涉及这些化合物或其药学上可接受的盐在治疗和预防上述疾病以及为此目的制备药物中的用途。

公开(公告)号：WO2011119518A1

公开(公告)日：2011-09-29

申请号：PCT/US2011/029294

申请日：2011-03-22

Applicant: MERCK SHARP & DOHME CORP. ,  RAGHAVAN, Subharekha ,  STELMACH, John ,  GUO, Jian ,  GROEPER, Jonathan ,  BROCKUNIER, Linda ,  ROSAUER, Keith ,  SHEN, Hong ,  LIANG, Rui ,  DING, Fa-Xiang ,  SCHMIDT, Darby

Inventor： RAGHAVAN, Subharekha ,  STELMACH, John ,  GUO, Jian ,  GROEPER, Jonathan ,  BROCKUNIER, Linda ,  ROSAUER, Keith ,  SHEN, Hong ,  LIANG, Rui ,  DING, Fa-Xiang ,  SCHMIDT, Darby

IPC: A01N43/54 ,  A61K31/505

CPC classification number: C07D403/14 ,  C07D401/14 ,  C07D403/04 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04 ,  C07D487/04

Abstract: The invention relates to compounds having the structure of Formula (I) and pharmaceutically acceptable salts thereof, which are soluble guanylate cyclase activators. The compounds are capable of modulating the body's production of cyclic guanosine monophosphate ("cGMP") and are generally suitable for the therapy and prophylaxis of diseases which are associated with a disturbed cGMP balance. The compounds are useful for treatment or prevention of cardiovascular diseases, endothelial dysfunction, diastolic dysfunction, atherosclerosis, hypertension, pulmonary hypertension, angina pectoris, thromboses, restenosis, myocardial infarction, strokes, cardiac insufficiency, pulmonary hypertonia, erectile dysfunction, asthma bronchiale, chronic kidney insufficiency, diabetes, or cirrhosis of the liver.

Abstract translation: 本发明涉及具有式（I）结构的化合物及其可药用盐，它们是可溶性鸟苷酸环化酶活化剂。 这些化合物能够调节人体的环鸟苷酸（“cGMP”）的产生，并且通常适用于治疗和预防与扰乱的cGMP平衡有关的疾病。 该化合物可用于治疗或预防心血管疾病，内皮功能障碍，舒张功能障碍，动脉粥样硬化，高血压，肺动脉高压，心绞痛，血栓形成，再狭窄，心肌梗死，中风，心功能不全，肺性高血压，勃起功能障碍，支气管哮喘，慢性 肾功能不全，糖尿病或肝硬化。

公开(公告)号：WO2006017055A3

公开(公告)日：2006-08-10

申请号：PCT/US2005023684

申请日：2005-07-01

Applicant: MERCK & CO INC ,  BEESON TERESA ,  BROCKUNIER LINDA ,  PARMEE EMMA R ,  RAGHAVAN SUBHAREKHA

Inventor： BEESON TERESA ,  BROCKUNIER LINDA ,  PARMEE EMMA R ,  RAGHAVAN SUBHAREKHA

IPC: A61K31/415 ,  C07D231/10 ,  C07D403/02

CPC classification number: C07D403/12 ,  C07D231/14 ,  C07D233/90 ,  C07D401/06 ,  C07D401/14 ,  C07D417/12

Abstract: Pyrazole amides are disclosed. The compounds are useful for treating type 2 diabetes and related conditions. Pharmaceutical compositions and methods of treatment are also included.

Abstract translation: 披露了吡唑酰胺。 这些化合物可用于治疗2型糖尿病和相关病症。 药物组合物和治疗方法也包括在内。

公开(公告)号：WO2017200857A1

公开(公告)日：2017-11-23

申请号：PCT/US2017/032310

申请日：2017-05-12

Applicant: MERCK SHARP & DOHME CORP. ,  BERGER, Raphaelle ,  DONG, Guizhen ,  RAGHAVAN, Subharekha ,  YANG, Zhiqiang

Inventor： BERGER, Raphaelle ,  DONG, Guizhen ,  RAGHAVAN, Subharekha ,  YANG, Zhiqiang

IPC: A61K31/505 ,  A61K31/519 ,  A61K45/06 ,  C07D235/00 ,  C07D249/16 ,  C07D519/00

Abstract: Provided are methods for treating or preventing a fibrotic disease selected from systemic sclerosis, cystic fibrosis, non-alcoholic steatohepatitis, Peyronie's disease, or interstitial lung disease; the method comprising administering a therapeutically effective amount of a compound of Formula (I) (wherein R 1 , R 2 , R 3 , R 4 , and R 5 are as herein described) or a pharmaceutically acceptable salt thereof, to a patient in need of such therapy.

Abstract translation: 提供用于治疗或预防选自系统性硬化症，囊性纤维化，非酒精性脂肪性肝炎，佩罗尼氏病或间质性肺病的纤维化疾病的方法; 该方法包括给予治疗有效量的式（I）化合物（其中R 1，R 2，R 3，R 4，R 5， R 4和R 5如本文所述）或其药学上可接受的盐给需要这种治疗的患者施用。

公开(公告)号：WO2016191335A1

公开(公告)日：2016-12-01

申请号：PCT/US2016/033693

申请日：2016-05-23

Applicant: MERCK SHARP & DOHME CORP. ,  GARFUNKLE, Joie ,  ORNOSKI, Olga ,  PARKER, Dann, L., Jr. ,  RAGHAVAN, Subharekha ,  XU, Libo ,  YANG, Zhiqiang

Inventor： GARFUNKLE, Joie ,  ORNOSKI, Olga ,  PARKER, Dann, L., Jr. ,  RAGHAVAN, Subharekha ,  XU, Libo ,  YANG, Zhiqiang

IPC: C07D487/04 ,  A61K31/519

CPC classification number: A61K31/519 ,  A61K45/06 ,  A61P1/16 ,  A61P3/10 ,  A61P9/04 ,  A61P9/12 ,  A61P11/06 ,  A61P13/12 ,  A61P15/10 ,  C07D519/00

Abstract: A compound of Formula I or a pharmaceutically acceptable salt thereof, are capable of modulating the body's production of cyclic guanosine monophosphate ("cGMP") and are generally suitable for the therapy and prophylaxis of diseases which are associated with a disturbed cGMP balance. The invention furthermore relates to processes for preparing compounds of Formula I, or a pharmaceutically acceptable salt thereof, for their use in the therapy and prophylaxis of the abovementioned diseases and for preparing pharmaceuticals for this purpose, and to pharmaceutical compositions which comprise compounds of Formula I or a pharmaceutically acceptable salt thereof.

Abstract translation: 式I化合物或其药学上可接受的盐能够调节身体产生环鸟苷酸（“cGMP”），并且通常适用于治疗和预防与受干扰的cGMP平衡有关的疾病。 本发明还涉及用于制备式I化合物或其药学上可接受的盐的方法，用于治疗和预防上述疾病和用于制备用于此目的的药物，以及包含式I化合物的药物组合物 或其药学上可接受的盐。

公开(公告)号：WO2011149921A1

公开(公告)日：2011-12-01

申请号：PCT/US2011/037718

申请日：2011-05-24

Applicant: MERCK SHARP & DOHME CORP. ,  RAGHAVAN, Subharekha ,  STELMACH, John, E. ,  SMITH, Cameron, J. ,  LI, Hong ,  WHITEHEAD, Alan ,  WADDELL, Sherman, T. ,  CHEN, Yi-Heng ,  MIAO, Shouwu ,  ORNOSKI, Olga, A. ,  GARFUNKLE, Joie ,  LIAO, Xibin ,  CHANG, Jiang ,  HAN, Xiaoqing ,  GUO, Jian ,  GROEPER, Jonathan, A. ,  BROCKUNIER, Linda, L. ,  ROSAUER, Keith ,  PARMEE, Emma, R.

Inventor： RAGHAVAN, Subharekha ,  STELMACH, John, E. ,  SMITH, Cameron, J. ,  LI, Hong ,  WHITEHEAD, Alan ,  WADDELL, Sherman, T. ,  CHEN, Yi-Heng ,  MIAO, Shouwu ,  ORNOSKI, Olga, A. ,  GARFUNKLE, Joie ,  LIAO, Xibin ,  CHANG, Jiang ,  HAN, Xiaoqing ,  GUO, Jian ,  GROEPER, Jonathan, A. ,  BROCKUNIER, Linda, L. ,  ROSAUER, Keith ,  PARMEE, Emma, R.

IPC: A01N43/90 ,  A61K31/519

CPC classification number: C07D487/04 ,  A61K31/519 ,  C07D519/00

Abstract: A compound of Formula (I): or a pharmaceutically acceptable salt thereof, are capable of modulating the body's production of cyclic guanosine monophosphate ("cGMP") and are generally suitable for the therapy and prophylaxis of diseases which are associated with a disturbed cGMP balance. The invention furthermore relates to processes for preparing compounds of Formula I, or a pharmaceutically acceptable salt thereof, for their use in the therapy and prophylaxis of the abovementioned diseases and for preparing pharmaceuticals for this purpose, and to pharmaceutical preparations which comprise compounds of Formula (I) or a pharmaceutically acceptable salt thereof.

Abstract translation: 式（I）的化合物或其药学上可接受的盐能够调节身体的环磷酸鸟苷（“cGMP”）的产生，并且通常适用于治疗和预防与受干扰的cGMP平衡相关的疾病 。 本发明还涉及用于制备式I化合物或其药学上可接受的盐的方法，用于治疗和预防上述疾病和用于制备用于此目的的药物以及包含式（III）化合物的药物制剂 I）或其药学上可接受的盐。

公开(公告)号：WO2007120575A2

公开(公告)日：2007-10-25

申请号：PCT/US2007/008584

申请日：2007-04-06

Applicant: MERCK & CO., INC. ,  COLLETTI, Steven, L. ,  TATA, James, R. ,  CHEN, Weichun ,  BERESIS, Richard, T. ,  DING, Fa-Xiang ,  SCHMIDT, Darby, Rye ,  SHEN, Hong ,  RAGHAVAN, Subharekha

Inventor： COLLETTI, Steven, L. ,  TATA, James, R. ,  CHEN, Weichun ,  BERESIS, Richard, T. ,  DING, Fa-Xiang ,  SCHMIDT, Darby, Rye ,  SHEN, Hong ,  RAGHAVAN, Subharekha

IPC: C07D487/14

CPC classification number: C07D333/38 ,  C07D277/56 ,  C07D333/40 ,  C07D413/14

Abstract: The present invention encompasses compounds of Formula (I) as well as pharmaceutically acceptable salts and hydrates thereof, that are useful for treating atherosclerosis, dysliptdemias and the like. Pharmaceutical compositions and methods of use are also included.

Abstract translation: 本发明包括式（I）化合物及其药学上可接受的盐和水合物，其可用于治疗动脉粥样硬化，排尿困难等。 还包括药物组合物和使用方法。

公开(公告)号：WO2016191334A1

公开(公告)日：2016-12-01

申请号：PCT/US2016/033692

申请日：2016-05-23

Applicant: MERCK SHARP & DOHME CORP. ,  GARFUNKLE, Joie ,  ORNOSKI, Olga ,  PARKER, Dann, L., Jr. ,  RAGHAVAN, Subharekha ,  XU, Libo

Inventor： GARFUNKLE, Joie ,  ORNOSKI, Olga ,  PARKER, Dann, L., Jr. ,  RAGHAVAN, Subharekha ,  XU, Libo

IPC: C07D487/04 ,  A61K31/519

CPC classification number: A61K31/519 ,  A61K45/06 ,  A61P9/08 ,  C07D519/00

Abstract: A compound of Formula I or a pharmaceutically acceptable salt thereof, are capable of modulating the body's production of cyclic guanosine monophosphate ("cGMP") and are generally suitable for the therapy and prophylaxis of diseases which are associated with a disturbed cGMP balance. The invention furthermore relates to processes for preparing compounds of Formula I, or pharmaceutically acceptable salt thereofs, for their use in the therapy and prophylaxis of the abovementioned diseases and for preparing pharmaceuticals for this purpose, and to pharmaceutical compositions which comprise compounds of Formula I or pharmaceutically acceptable salts thereof.

Abstract translation: 式I化合物或其药学上可接受的盐能够调节身体产生环鸟苷酸（“cGMP”），并且通常适用于治疗和预防与受干扰的cGMP平衡有关的疾病。 本发明还涉及用于制备式I化合物或其药学上可接受的盐的方法，用于治疗和预防上述疾病和用于制备用于此目的的药物，以及包含式I化合物或 其药学上可接受的盐。

公开(公告)号：WO2015187470A1

公开(公告)日：2015-12-10

申请号：PCT/US2015/033084

申请日：2015-05-29

Applicant: MERCK SHARP & DOHME CORP. ,  CAMPBELL, Brian, T. ,  DONG, Guizhen ,  GARFUNKLE, Joie ,  KIM, Alexander ,  ORNOSKI, Olga ,  PARKER, Dann, L., Jr. ,  RAGHAVAN, Subharekha ,  XU, Libo ,  YANG, Zhiqiang

Inventor： CAMPBELL, Brian, T. ,  DONG, Guizhen ,  GARFUNKLE, Joie ,  KIM, Alexander ,  ORNOSKI, Olga ,  PARKER, Dann, L., Jr. ,  RAGHAVAN, Subharekha ,  XU, Libo ,  YANG, Zhiqiang

IPC: C07D487/04

CPC classification number: C07D519/00 ,  A61K31/519 ,  A61K31/5377 ,  A61K31/541 ,  A61K45/06

Abstract: A compound of Formula II or a pharmaceutically acceptable salt thereof, are capable of modulating the body's production of cyclic guanosine monophosphate ("cGMP") and are generally suitable for the therapy and prophylaxis of diseases which are associated with a disturbed cGMP balance. The invention furthermore relates to processes for preparing compounds of Formula II, or a pharmaceutically acceptable salt thereof, for their use in the therapy and prophylaxis of the abovementioned diseases and for preparing pharmaceuticals for this purpose, and to pharmaceutical preparations which comprise compounds of Formula II or a pharmaceutically acceptable salt thereof.

Abstract translation: 式II化合物或其药学上可接受的盐能够调节身体产生环鸟嘌呤一磷酸（“cGMP”），并且通常适用于治疗和预防与受干扰的cGMP平衡有关的疾病。 本发明还涉及用于制备式II化合物或其药学上可接受的盐的方法，用于治疗和预防上述疾病和用于制备用于该目的的药物以及包含式II化合物的药物制剂 或其药学上可接受的盐。

公开(公告)号：WO2007120575A3

公开(公告)日：2008-10-09

申请号：PCT/US2007008584

申请日：2007-04-06

Applicant: MERCK & CO INC ,  COLLETTI STEVEN L ,  TATA JAMES R ,  CHEN WEICHUN ,  BERESIS RICHARD T ,  DING FA-XIANG ,  SCHMIDT DARBY RYE ,  SHEN HONG ,  RAGHAVAN SUBHAREKHA

Inventor： COLLETTI STEVEN L ,  TATA JAMES R ,  CHEN WEICHUN ,  BERESIS RICHARD T ,  DING FA-XIANG ,  SCHMIDT DARBY RYE ,  SHEN HONG ,  RAGHAVAN SUBHAREKHA

IPC: C07D333/02 ,  A61K31/381 ,  A61K31/425 ,  C07D327/06

CPC classification number: C07D333/38 ,  C07D277/56 ,  C07D333/40 ,  C07D413/14

Abstract: The present invention encompasses compounds of Formula (I) as well as pharmaceutically acceptable salts and hydrates thereof, that are useful for treating atherosclerosis, dysliptdemias and the like. Pharmaceutical compositions and methods of use are also included.

Abstract translation: 本发明包括式（I）化合物及其药学上可接受的盐和水合物，它们可用于治疗动脉粥样硬化，排尿困难等。 还包括药物组合物和使用方法。